G2Cdb::Human Disease report

Disease id
D00000294
Name
McCune-Albright syndrome
Nervous system disease
no

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001473 GNAS
GNAS complex locus
Y (12199346) Microinsertion (MI) Y
G00001473 GNAS
GNAS complex locus
Y (15126527) Microinsertion (MI) Y

References

  • Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome--a European Collaborative Study.

    Lumbroso S, Paris F, Sultan C and European Collaborative Study

    Service d'Hormonologie, Hôpital Lapeyronie, Centre Hospitalier Universitaire (CHU) de Montpellier and Institut National de la Santé et de la Recherche Médicale, Montpellier, France 34295.

    McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and peripheral precocious puberty. It is due to postzygotic activating mutations of arginine 201 in the guanine-nucleotide-binding protein (G protein) alpha-subunit (Gsalpha), leading to a mosaic distribution of cells bearing constitutively active adenylate cyclase. MAS is heterogeneous: beyond the classic triad, a number of atypical or partial presentations have been reported. We present here the results of a systematic search for Gsalpha mutations in patients presenting with at least one of the signs of MAS, using a PCR-based sensitive method. We studied 113 patients (98 girls and 15 boys), 24% presenting the classic triad, 33% with two signs, and 40% with only one classic sign. Overall, the mutation was identified in 43% of the patients. When an affected tissue was available, the mutation was found in more than 90% of the patients, whatever the number of signs. Skin was a noteworthy exception because only three of the 11 skin samples were positive. The mutation was detected in 46% of blood samples in patients presenting the classic triad, whereas this figure fell to 21% and 8% in patients with two and one sign, respectively. Our results highlight the frequency of partial forms of MAS and the usefulness of sensitive techniques to confirm the diagnosis at the molecular level. It should be emphasized that we found the mutation in 33% of the 39 cases of isolated peripheral precocious puberty. This study has further widened the definition of MAS. Affections as clinically different as monostotic fibrous dysplasia, isolated peripheral precocious puberty, neonatal liver cholestasis, and the classic MAS all appear to be components of a wide spectrum of diseases based on the same molecular defect.

    The Journal of clinical endocrinology and metabolism 2004;89;5;2107-13

  • Searching for Arg201 mutations in the GNAS1 gene in Italian patients with McCune-Albright syndrome.

    de Sanctis L, Romagnolo D, Greggio N, Genitori L, Lala R and de Sanctis C

    Department of Pediatrics, University of Torino, Regina Margherita Children's Hospital, Italy. ldesanct@pediatria.unito.it

    McCune-Albright syndrome (MAS) is a rare disease caused by somatic postzygotic mutations at Arg201 in the GNAS1 gene that encodes for the Gsalpha protein. Arg201 mutations are gain-of-function mutations in affected tissues (including bone, skin, endocrine glands and other tissues) that result in the activation of cAMP. We used a polymerase chain reaction(PCR)-based technique for the selective enrichment and analysis of the Arg201 mutant allele in 27 different tissues from 24 Italian patients with one or more signs of MAS. Arg201 mutations were identified in 13 different tissues (48.1%) from 11 patients (45.8%). Mutation detection rates differed across the various types of tissue samples, and the mutation was not always found in every tissue sample from the same patient. To overcome problems in the analysis of mutations in somatic mosaicism, as occurs in MAS, a highly sensitive molecular technique should be applied, the most appropriate tissue source selected, and various affected tissues from the same patient analyzed.

    Journal of pediatric endocrinology & metabolism : JPEM 2002;15 Suppl 3;883-9

Literature (2)

Pubmed - other

  • Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome--a European Collaborative Study.

    Lumbroso S, Paris F, Sultan C and European Collaborative Study

    Service d'Hormonologie, Hôpital Lapeyronie, Centre Hospitalier Universitaire (CHU) de Montpellier and Institut National de la Santé et de la Recherche Médicale, Montpellier, France 34295.

    McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and peripheral precocious puberty. It is due to postzygotic activating mutations of arginine 201 in the guanine-nucleotide-binding protein (G protein) alpha-subunit (Gsalpha), leading to a mosaic distribution of cells bearing constitutively active adenylate cyclase. MAS is heterogeneous: beyond the classic triad, a number of atypical or partial presentations have been reported. We present here the results of a systematic search for Gsalpha mutations in patients presenting with at least one of the signs of MAS, using a PCR-based sensitive method. We studied 113 patients (98 girls and 15 boys), 24% presenting the classic triad, 33% with two signs, and 40% with only one classic sign. Overall, the mutation was identified in 43% of the patients. When an affected tissue was available, the mutation was found in more than 90% of the patients, whatever the number of signs. Skin was a noteworthy exception because only three of the 11 skin samples were positive. The mutation was detected in 46% of blood samples in patients presenting the classic triad, whereas this figure fell to 21% and 8% in patients with two and one sign, respectively. Our results highlight the frequency of partial forms of MAS and the usefulness of sensitive techniques to confirm the diagnosis at the molecular level. It should be emphasized that we found the mutation in 33% of the 39 cases of isolated peripheral precocious puberty. This study has further widened the definition of MAS. Affections as clinically different as monostotic fibrous dysplasia, isolated peripheral precocious puberty, neonatal liver cholestasis, and the classic MAS all appear to be components of a wide spectrum of diseases based on the same molecular defect.

    The Journal of clinical endocrinology and metabolism 2004;89;5;2107-13

  • Searching for Arg201 mutations in the GNAS1 gene in Italian patients with McCune-Albright syndrome.

    de Sanctis L, Romagnolo D, Greggio N, Genitori L, Lala R and de Sanctis C

    Department of Pediatrics, University of Torino, Regina Margherita Children's Hospital, Italy. ldesanct@pediatria.unito.it

    McCune-Albright syndrome (MAS) is a rare disease caused by somatic postzygotic mutations at Arg201 in the GNAS1 gene that encodes for the Gsalpha protein. Arg201 mutations are gain-of-function mutations in affected tissues (including bone, skin, endocrine glands and other tissues) that result in the activation of cAMP. We used a polymerase chain reaction(PCR)-based technique for the selective enrichment and analysis of the Arg201 mutant allele in 27 different tissues from 24 Italian patients with one or more signs of MAS. Arg201 mutations were identified in 13 different tissues (48.1%) from 11 patients (45.8%). Mutation detection rates differed across the various types of tissue samples, and the mutation was not always found in every tissue sample from the same patient. To overcome problems in the analysis of mutations in somatic mosaicism, as occurs in MAS, a highly sensitive molecular technique should be applied, the most appropriate tissue source selected, and various affected tissues from the same patient analyzed.

    Journal of pediatric endocrinology & metabolism : JPEM 2002;15 Suppl 3;883-9

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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